Tibsovo(ivosidenib)

Tibsovo (ivosidenib) is a drug for which a CHMP positive opinion for marketing authorisation was issued on 23 February 2023. It received Orphan medicinal product designation for acute myeloid leukaemia on 12 December 2016 and for biliary tract cancer on 21 March 2018. The recommended dose for Tibsovo is 500 mg.

Efficacy findings include a median PFS of 2.7 months and 1.4 months, with a PFS HR of 0.37 (p-value <0.0001). Median OS was 10.3 months and 7.5 months, with an OS HR of 0.79 (p-value 0.093). The maximum 2-HG inhibition in AML patients was 90%. In the ivosidenib + azacitidine arm for AML, 2-HG inhibition was 80%. The ORR was 2.4% and 0%. There was an inverse relationship between exposure and OR (p-value 0.03).

Safety concerns include a predicted QTc prolongation of 19.8 msec for mean Cmax in CCA patients and 31.3 msec for max Cmax in CCA patients. The upper limit of the 90% prediction interval on QTc prolongation was 19.7 msec for hematological malignancies, 18.9 msec for acute myeloid leukemia, and 20.6 msec for cholangiocarcinoma. The incidence of treatment-emergent adverse events leading to treatment interruption was 30.1% and 18.6%, with a frequency of dose interruption due to adverse reactions of 16%.